The biological diagnosis of certain vertically transmitted diseases in the newborn is particularly difficult when the available methods of antigen detection are not reliable. Indeed, serological tests cannot be carried out in infants due to the presence, up to the age of 6 months, of maternal antibodies transmitted during pregnancy (Simister et al., J. Reprod. Immun., 1997, 37: 1-23; Williams et al., Arch. Dis. Childhood, 1969, 44: 511-514), which prevents assessment of the proportion of antibodies generated by the child. Preemptive treatments, which are not devoid of toxicity or of undesirable effects, are therefore administered, from birth, to a newborn suspected of a congenital disease. These treatments are maintained until the child is at least 6 months old and/or until it is possible to carry out a serological examination allowing assay of only the child's antibodies, once the antibodies transmitted from the mother have been completely eliminated.
This is, for example, the case of Chagas disease, also known as South American trypanosomiasis, a parasitic infection caused by Trypanosoma cruzi, which is rife in the tropical regions of South America and Central America. In some neonates, congenital Chagas disease can be diagnosed by microscopic examination of the parasite in a blood sample and/or by amplification of portions of parasitic genes by PCR (Schijman et al., J. Antimicrob. Chemother., 2003, 52: 441-449). However, these techniques are limited by obstacles that prevent from reaching a definitive diagnostic conclusion. These obstacles are notably linked to thresholds that are too high for the sensitivity of microscopic detection, presenting a risk of a false-negative diagnosis, and to PCR amplification of DNA derived from fragments of soluble parasitic genetic material that have crossed the placental barrier (rather than from viable parasites), presenting a risk of a false-positive diagnosis. It is therefore necessary to carry out a serological test 6 to 9 months after birth to rule out the presence of any undetected infection (Chippaux et al., Tropical Med. International Health, 2010, 15: 87-93). Due to the limitations of the available diagnostic techniques, treatment based on benznidazole is administered preemptively to the newborn immediately after birth. Although early administration favors both efficacy and tolerability of benznidazole, this substance is toxic, induces many side-effects, and cannot be administered without follow-up medical supervision. Moreover, such a treatment represents a considerable cost for the families affected by this disease, occurring in countries with low economic strength.
A similar problem is encountered in the case of toxoplasmosis, a parasitic infection caused by the protozoan Toxoplasma gondii. Although infection by this parasite occurs in all regions of the world, it is more prevalent in certain parts of Europe, the Caribbean and South America than in Asia, the United States or Australia. Congenital infection can be diagnosed by PCR, and a Western blot qualitative test is used for comparing the immunological profiles of the IgM and IgG from the mother and the child, without determining the amounts of immunoglobulins (Pinon et al., J. Clin. Microbiol., 2001, 39: 2267-2271). However, this test requires maternal plasma to be collected shortly after birth, and its use is therefore exclusively perinatal. Conversely, measurement by enzyme immunoassay (EIA) of the differences between the avidity of the antibodies of the mother and those of the child can only be performed about 6 months after birth. To overcome these shortcomings, effective but aggressive treatment with pyrimethamine and sulphonamides is administered to the newborn preemptively. However, without close medical supervision this treatment can have dramatic side-effects.
Malaria is another example of parasitic disease for which understanding of the mechanisms of acquisition of specific natural immunity by the infant might be of help for proposing public health measures for protecting groups at risk and for better targeting future strategies of antimalarial vaccination. Malaria is due to a parasite of the genus Plasmodium, of which the species Plasmodium falciparum is the most common and the most pathogenic in humans and that which is responsible for fatal cases. Malaria affects about a hundred countries in the world, particularly in the underprivileged tropical zones of Africa, Asia and Latin America. It mainly affects children under 5 years of age and pregnant women, who are particularly vulnerable because the placenta constitutes a target where the parasites may accumulate. In a pregnant woman, malarial infection can cause a whole range of detrimental effects: spontaneous abortion, premature birth, low birth weight, congenital transmission, and neonatal death.
In all these cases of vertically transmitted infectious diseases, it therefore seems to be crucial to develop new strategies for accurate and definitive diagnosis of a congenital disease in the first months of life of the newborn. An early biological diagnosis of these infections could provide valuable assistance in the decision of whether to initiate or curtail drug treatments, with a benefit in terms of children's health, but also to combat these diseases and their consequences.